Controlled drug delivery occurs when a polymer, whether natural or synthetic, is judiciously combined with a bioactive agent in such a way that the bioactive agent is released from the material in a predesigned manner. The release of the bioactive agent may be constant over a long period, it may be cyclic over a long period, or it may be triggered by the environment or other external events.
Providing control over drug delivery can be very important at times when traditional oral or injectable drug formulations cannot be used. These include situations requiring the slow release of water-soluble drugs, the fast release of hydrophobic drugs, drug delivery to specific sites, drug delivery using nanoparticulate systems, delivery of two or more agents with the same formulation, and systems based on carriers that can dissolve or degrade and be readily eliminated. The ideal drug delivery system should be inert, biocompatible, mechanically strong, comfortable for the patient, capable of achieving high drug loading, safe from accidental release, simple to administer and remove, and easy to fabricate and sterilize.
To be successfully used in controlled drug delivery formulations, a polymeric material must be chemically inert and free of leachable impurities. It must also have an appropriate physical structure, with minimal undesired aging, and be readily processable. Some of the polymers that are currently being used or studied for controlled drug delivery include: poly(2-hydroxy ethyl methacrylate); poly(N-vinyl pyrrolidone); poly(methyl methacrylate); poly(vinyl alcohol; poly(acrylic acid); polyacrylamide; poly(hydroxypropylmethacrylamide) poly(ethylene-co-vinyl acetate); poly(ethylene glycol); poly(methacrylic acid).
However, in recent years additional polymers designed primarily for medical applications have entered the arena of controlled release. Many of these materials are designed to degrade within the body, among them: polylactides (PLA); Polyglycolides (PGA); poly(lactide-co-glycolides) (PLGA); polyanhydrides; polyorthoesters.
Up to 40% of lipophilic drug candidates fail to reach the market although exhibiting interesting pharmacodynamic activities. Various formulation strategies have been investigated to improve the solubility and the rate of dissolution and hence the oral bioavailability of lipophilic drugs. These strategies include solubilization, addition of surfactants, use of different polymorphic/amorphic drug forms, reduction of drug particle size and complexation.
Non-traditional technologies for improving the solubility and dissolution of lipohilic drugs, including drug-polymer solid solutions and solid dispersions, have gained increasing attention. The pharmaceutical application of solid solutions/dispersions to enhance oral bioavailability was first envisioned in 1961. Since then, only five commercial products have been launched that use the solid solution/dispersion approach.
Different water-soluble polymeric excipients have been employed as carriers of solid solutions/dispersions. Among them, polyethylene glycols (PEG, Mw 1500-20,000) are most commonly used due to their good solubility in water and in many organic solvents, low melting points (under 65° C.), ability to solubilize some compounds and improvement of compound wettability. Other polymeric carriers that have been suggested as carriers in solid solutions/dispersions include polyvinyl pyrrolidone (PVP), polyvinylalcohol (PVA), polyvinyl-pyrrolidone polyvinylacetate copolymer (PVP-PVA), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyurethanes, Poloxamer 407 and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®, BASF).
The use of poly(2-oxazoline)s in drug delivery systems and dental formulations is known from the prior art.
WO 2009/156180, which was published after the priority date of the present application, describes a composition, comprising:    (a) at least one copolymer comprising repeating units of formula (I) (CH2)2NCORA with RA being selected such that the repeating unit of formula (I) is hydrophilic; and repeating units of the formula (II) (CH2)2NCORB with RB being selected such that the repeating unit of formula (II) is more hydrophobic than the repeating unit of formula (I); and    (b) one or more active agent(s).
WO 02/26179 describes a pain relief composition as an implantable pellet form and a method to relieve pain using such implantable pellets in which formulations comprise one or more anesthetic agents in combination with one or more analgesic agents and excipients like polyethylene glycol, starch, dextran, polyvinylalcohol, poly(2-ethyl-2-oxazoline) and mixtures thereof. The pellets are not intended for oral application. There is no referral to the preparation of solid solutions nor solid amorphous suspensions including the API.
U.S. Pat. No. 6,730,321 describes a drug delivery system suitable for oral administration that facilitates a pulsatile release of the active agent. Poly(2-oxazoline) is mentioned as a possible co-excipient to be used in the formulation.
U.S. Pat. No. 5,536,505 describes a controlled release matrix system comprising a homogenous mixture of poly(2-ethyl-2-oxazoline) and cellulose acetate, and of a water-soluble active ingredient, wherein said cellulose acetate is present in the amount of 95 to 20 weight % and the poly(2-ethyl-2-oxazoline) is present in the amount of 5 to 80 weight %, based on the total weight percentages of the poly(2-ethyl-2-oxazoline) and cellulose acetate equaling 100 weight %, and wherein said active ingredient is present in the amount of 0.01 to 40 weight % based on the total weight percentages of poly(2-ethyl-2-oxazoline), cellulose acetate and active ingredient equaling 100 weight %. It is stated that, poly(2-ethyl-2-oxazoline) is compatible with the cellulose acetate of the invention in that it is capable of yielding a clear film and one glass transition temperature by either differential scanning calorimetry or dynamic mechanical thermal analysis.
U.S. Pat. No. 4,990,339 describes an aqueous soluble dermal treatment film which comprises: (a) a structural layer comprising a poly(2-alkyl-2-oxazoline) polymer; and (b) a pressure sensitive adhesive layer comprising 10-75 wt. % of a poly(2-alkyl-2-oxazoline) polymer, 10-75 wt. % of a functional diluent comprising a hydroxy compound or a carboxylic acid compound; and 5-35 wt. % of a compatible tackifier
US 2007/0183987 describes a dental whitening composition and a bleaching gel comprising poly(2-ethyl-2-oxazoline) and a peroxide.